Single-nucleotide polymorphisms in DNA repair genes and association with breast cancer risk in the web study

Abstract

Base excision repair (BER) and nucleotide excision repair (NER) pathways repair damaged DNA, and polymorphisms in these genes might affect breast cancer susceptibility. We evaluated associations between seven single-nucleotide polymorphisms in four DNA repair genes (ERCC4 rs1799801, XPC rs2227998, rs2228001, rs2228000, OGG1 rs1052133 and XRCC1 rs25487 and rs25486) and breast cancer risk, examining modification by smoking and alcohol consumption, using data from the Western New York Exposures and Breast Cancer Study. Women aged 35-79 years with incident breast cancer (n = 1170) and age- and race-matched controls (n = 2115) were enrolled. Genotyping was performed using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). No significant associations were observed in premenopausal women. Among postmenopausal women, rs25487 and rs25486 (OR = 1.24; 95% CI 1.01-1.51 and OR = 1.23; 95% CI 1.01-1.49, respectively, for combined heterozygous and homozygous variant compared with reference) were associated with increased risk of breast cancer. Postmenopausal women carrying the variant allele of the synonymous XPC polymorphism (rs2227998) were also at borderline significantly increased risk (OR = 1.24; 95% CI 1.01-1.52, heterozygous variant compared with reference; OR = 1.22; 95% CI 1.01-1.48, for combined heterozygous and homozygous variant compared with reference). There was no evidence of genotype-smoking and genotype-alcohol consumption interactions for pre- and postmenopausal women. These results indicate that some of the variants in BER and NER genes may influence risk of postmenopausal breast cancer.

Association of Genetic Variations in XRCC1 and ERCC1 Genes with Sporadic Breast Cancer

“…Previous investigations have reported that the genetic variants of the XRCC1 (rs25487) gene are associated with the risk of BC (22,23 (27). Taken together, the current results did not suggest that the XRCC1 gene polymorphism plays a significant role in the initiation of BC.…”

Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population

“…Similarly, another metaanalysis of XRCC1 polymorphisms and their association with breast cancer risk found that the 399Gln allele might act as a recessive allele in its association with breast cancer risk (Saadat and Ansari-Lari, 2009). In addition, this polymorphism has been associated with an increased risk of breast cancer in Caucasian (Roberts et al, 2011), Iranian (Saadat et al, 2008), and Portuguese (Silva et al, 2007) postmenopausal women.…”

Polymorphisms in the DNA Repair GeneERCC2/XPDand Breast Cancer Risk: A HapMap-Based Case–Control Study Among Han Women in a Chinese Less-Developed Area

“…More recently, Samson et al (2011) reported that the XPD Gln/Gln genotype is significantly associated with an increased risk of breast cancer in south Indian women. Similarly, Roberts et al (2011) concluded that variants in base excision repair and NER genes might influence a person's risk of developing breast cancer. Smith et al (2008) also suggested that individual DNA repair genotypes may have a small effect on breast cancer risk; however, there is a combined effect of multiple DNA repair genotypes from different pathways on the breast cancer risk.…”